Effectiveness of Artemisinin Combination Regimens in Falciparum Malaria (ACT)
|ClinicalTrials.gov Identifier: NCT00902811|
Recruitment Status : Unknown
Verified May 2009 by Medecins Sans Frontieres, Netherlands.
Recruitment status was: Recruiting
First Posted : May 15, 2009
Last Update Posted : May 15, 2009
Antimalarial drug resistance is increasing nearly everywhere in the tropical world, confounding global attempts to "Roll Back Malaria." South East Asia has the most resistant malaria parasites in the world. This has limited the options for treatment in this region.
Artemisinin-based combination therapy is now the recommended treatment for uncomplicated falciparum malaria. The success of this policy change in practice will depend on the efficacy of the components of the combination used, the population coverage achieved, high levels of adherence to treatment, low cost of the drugs, and preferably the drugs in a combination treatment should be formulated in a single tablet, to prevent one drug being taken without the partner drug. Until recently there were only two artemisinin-based fixed combinations available, artemether-lumefantrine and dihydroartemisinin-piperaquine; and only the former has international registration. More fixed combinations are needed urgently.
|Condition or disease||Intervention/treatment||Phase|
|Uncomplicated Falciparum Malaria||Drug: AM(FDC) Drug: AM(LT) Drug: AL Drug: DP Drug: AA(FDC)||Phase 4|
Malaria in Myanmar:
In Myanmar, malaria is the number one cause of morbidity. According to the Department of Health (DoH) and WHO there are approximately 500,000 patients with malaria each year. About 80% of reported infections are due to Plasmodium falciparum and 20% are due to Plasmodium vivax. This is likely to be a severe underestimation. MSF-Holland alone treats already 250,000 slide positive malaria patients per year in an area of mixed endemicity covering a population of less that 1 million patients out of a total population of 54 million in the country.
Chloroquine was the first line treatment for falciparum malaria for the last five decades. In 1996 and 1998 MSF-Holland with support from the Wellcome Trust (Prof N. White) performed studies in the northern and western part of the country, in which very high in-vivo resistance levels to chloroquine and sulfadoxine-pyrimethamine were demonstrated1,2. Combination treatment of mefloquine plus artesunate (loose tablets) [MA(LT)]and treatment with dihydroartemisinin-piperaquine (DP) both proved highly efficacious (99-100%)3,4. The studies performed by MSF provided an important component of the evidence used to convince the health authorities that a change of national protocol was needed. In 2001, the DOH of Myanmar changed the national protocol for the treatment of uncomplicated falciparum malaria; a 3 day treatment of mefloquine-artesunate was chosen to become the first line treatment. Artemether-lumefantrine (AL) and DP are also mentioned in the national protocol as effective treatment regimens, but there is a call in the protocol for more research of these treatments.
These changes in policy are a very good step forward and were widely respected. In practice, some problems remain.
MSF has implemented large malaria activities in Myanmar over the past decade. The programme has performed a diagnostic test for malaria for approximately 3,000,000 patients and approximately 1,500,000 patients have been treated with artemisinin combination treatment (ACT).
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||600 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Comparing the Effectiveness of 5 Artemisinin Combination Treatment Regimens in the Treatment of Uncomplicated Falciparum Malaria|
|Study Start Date :||December 2008|
|Estimated Primary Completion Date :||October 2009|
|Estimated Study Completion Date :||December 2009|
Active Comparator: AM(LT)
Artesunate (Arsumax®, Sanofi)
Artesunate (Arsumax®, Sanofi) 50 mg tabs given at 4 mg/Kg/day on day 0, day 1 and day 2 (total 12 mg/Kg) PLUS Mefloquine 250 mg base tabs given at 25 mg/Kg on day 0. Treatment is given in three equally divided daily doses to the nearest quarter tablet.
Other Name: Lariam®, Roche
Artesunate-mefloquine fixed dose combination
Artesunate-mefloquine fixed dose combination (artesunate 25mg/mefloquine hydrochloride 55mg, or artesunate 100mg/mefloquine hydrochloride 220mg), according to age-group.
Other Name: Far-Manguinhos, Brazil
artemether 20 mg - lumefantrine 120 mg co-formulated tabs
Coartem®: artemether 20 mg - lumefantrine 120 mg co-formulated tabs (Coartem®, Novartis) given as six twice-daily doses over three days, according to weight-groups. The second dose should be taken 6 to 10 hours after the first dose, given at inclusion. Patients will be advised to take some fatty food (or encouraged to give breast feeding) before each dose is taken. Fatty food or milk will not be provided by the researchers.
Other Name: Coartem®
40 mg dihydroartemisinin/320 mg piperaquine tablets and Dihydropiperaquine 20mg/Piperaquine 160 mg tablets
40 mg dihydroartemisinin/320 mg piperaquine tablets and Dihydropiperaquine 20mg/ Piperaquine 160 mg tablets),. Treatment is given according to age groups. In the age group <6yrs of age, a subdivision according to weight is made
Other Name: DuoCotecxin, Holley Pharm
Experimental: AA (FDC)
Artesunate-amodiaquine fixed dose combination
Artesunate-amodiaquine fixed dose combination (FDC) (Artesunate Amodiaquine Winthrop® Sanofi Aventis); Artesunate 25mg/amodiaquine 67.5mg; Artesunate 50mg/amodiaquine 135mg ; Artesunate 100mg/amodiaquine 270mg
Other Name: Artesunate Amodiaquine Winthrop® Sanofi Aventis
- Cure rate [ Time Frame: 63 days ]
- Early treatment failure [ Time Frame: Day 6 ]
- Late treatment failure [ Time Frame: Day 63 ]
- Adequate response [ Time Frame: Day 63 ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00902811
|Contact: Frank Smithuis, MDfirstname.lastname@example.org|
|Contact: Phaikyeong Cheah, PhDemail@example.com|
|Dabhine and Mingan Clinic||Recruiting|
|Sittwe, Rakhine, Myanmar|
|Contact: Pyay Phyo Aung firstname.lastname@example.org|
|Principal Investigator: Pyay Phyo Aung, MD|
|Myit Kyi Nar Clinic||Recruiting|
|Contact: Mya Nee Nyo email@example.com|
|Principal Investigator: Mya Nee Nyo, MD|
|Myothugyi Rural Health Center, Bu Thee Daung||Recruiting|
|Contact: Arkar Linn Naing firstname.lastname@example.org|
|Principal Investigator: Arkar Linn Naing, MD|
|Contact: Naing Nyo, MD|
|Principal Investigator: Naing Zaw, MD|
|Principal Investigator:||Frank Smithuis, MD||Medecins Sans Frontieres, Netherlands|